Dataset Information

Longitudinal changes in diffusion tensor-based quantitative MRI in multiple sclerosis.

ABSTRACT:

Objective

To estimate longitudinal changes in a quantitative whole-brain and tract-specific MRI study of multiple sclerosis (MS), with the intent of assessing the feasibility of this approach in clinical trials.

Methods

A total of 78 individuals with MS underwent a median of 3 scans over 2 years. Diffusion tensor imaging indices, magnetization transfer ratio, and T2 relaxation time were analyzed in supratentorial brain, corpus callosum, optic radiations, and corticospinal tracts by atlas-based tractography. Linear mixed-effect models estimated annualized rates of change for each index, and sample size estimates for potential clinical trials were determined.

Results

There were significant changes over time in fractional anisotropy and perpendicular diffusivity in the supratentorial brain and corpus callosum, mean diffusivity in the supratentorial brain, and magnetization transfer ratio in all areas studied. Changes were most rapid in the corpus callosum, where fractional anisotropy decreased 1.7% per year, perpendicular diffusivity increased 1.2% per year, and magnetization transfer ratio decreased 0.9% per year. The T2 relaxation time changed more rapidly than diffusion tensor imaging indices and magnetization transfer ratio but had higher within-participant variability. Magnetization transfer ratio in the corpus callosum and supratentorial brain declined at an accelerated rate in progressive MS relative to relapsing-remitting MS. Power analysis yielded reasonable sample sizes (on the order of 40 participants per arm or fewer) for 1- or 2-year trials.

Conclusions

Longitudinal changes in whole-brain and tract-specific diffusion tensor imaging indices and magnetization transfer ratio can be reliably quantified, suggesting that small clinical trials using these outcome measures are feasible.

SUBMITTER: Harrison DM

PROVIDER: S-EPMC3030233 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

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Publications

Longitudinal changes in diffusion tensor-based quantitative MRI in multiple sclerosis.

Harrison D M DM Caffo B S BS Shiee N N Farrell J A D JA Bazin P-L PL Farrell S K SK Ratchford J N JN Calabresi P A PA Reich D S DS

Neurology 20110101 2

<h4>Objective</h4>To estimate longitudinal changes in a quantitative whole-brain and tract-specific MRI study of multiple sclerosis (MS), with the intent of assessing the feasibility of this approach in clinical trials.<h4>Methods</h4>A total of 78 individuals with MS underwent a median of 3 scans over 2 years. Diffusion tensor imaging indices, magnetization transfer ratio, and T2 relaxation time were analyzed in supratentorial brain, corpus callosum, optic radiations, and corticospinal tracts b ...[more]

PMID: 21220722

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Project description:Diffusion magnetic resonance imaging can reveal quantitative information about the tissue changes in multiple sclerosis. The recently developed multi-compartment spherical mean technique can map different microscopic properties based only on local diffusion signals, and it may provide specific information on the underlying microstructural modifications that arise in multiple sclerosis. Given that the lesions in multiple sclerosis may reflect different degrees of damage, we hypothesized that quantitative diffusion maps may help characterize the severity of lesions "in vivo" and correlate these to an individual's clinical profile. We evaluated this in a cohort of 59 multiple sclerosis patients (62% female, mean age 44.7 years), for whom demographic and disease information was obtained, and who underwent a comprehensive physical and cognitive evaluation. The magnetic resonance imaging protocol included conventional sequences to define focal lesions, and multi-shell diffusion imaging was used with b-values of 1000, 2000 and 3000 s/mm2 in 180 encoding directions. Quantitative diffusion properties on a macro- and micro-scale were used to discriminate distinct types of lesions through a k-means clustering algorithm, and the number and volume of those lesion types were correlated with parameters of the disease. The combination of diffusion tensor imaging metrics (fractional anisotropy and radial diffusivity) and multi-compartment spherical mean technique values (microscopic fractional anisotropy and intra-neurite volume fraction) differentiated two type of lesions, with a prediction strength of 0.931. The B-type lesions had larger diffusion changes compared to the A-type lesions, irrespective of their location (P < 0.001). The number of A and B type lesions was similar, although in juxtacortical areas B-type lesions predominated (60%, P < 0.001). Also, the percentage of B-type lesion volume was higher (64%, P < 0.001), indicating that these lesions were larger. The number and volume of B-type lesions was related to the severity of disease evolution, clinical disability and cognitive decline (P = 0.004, Bonferroni correction). Specifically, more and larger B-type lesions were correlated with a worse Multiple Sclerosis Severity Score, cerebellar function and cognitive performance. Thus, by combining several microscopic and macroscopic diffusion properties, the severity of damage within focal lesions can be characterized, further contributing to our understanding of the mechanisms that drive disease evolution. Accordingly, the classification of lesion types has the potential to permit more specific and better-targeted treatment of patients with multiple sclerosis.

Project description:Registration of subject and control brains to a common anatomical space or template is the basis for quantitatively delineating regions of abnormality in an individual brain. Normally, a brain atlas is chosen as the template. Limitations in the registration process result in persistent differences between individual subject brains and template, which can be a source of error in an analysis. We propose a new approach to the registration process where the subject of interest is the registration template. Through this change, we eliminate errors due to differences between a brain template and a subject's brain. We applied this method to the analysis of FA values derived from DTI data of 20 individual mTBI patients as compared to 48 healthy controls. Subject-centered analysis resulted in identification of significantly fewer regions of abnormally low FA compared to two separate atlas-centered analyses, with subject-centered abnormalities essentially representing the common subset of abnormal low FA regions detected by the two atlas-centered methods. Whereas each atlas-centered approach demonstrated abnormalities in nearly every subject (19/20 and 20/20), the subject-centered approach demonstrated abnormalities in fewer than half the subjects (9/20). This reduction of diffusion abnormalities observed using the subject-centered approach is due to elimination of misregistration errors that occur when registering the subject of interest to a template. Evaluation of atlas-centered analyses demonstrated that 9.8% to 13.3% of subject GM and CSF was misregistered onto the WM of the brain atlas, resulting in the observation of additional low FA clusters compared to the subject-centered approach. Without careful evaluation, these misregistrations could be misinterpreted as pathology. An additional benefit of the subject-centered approach is that diffusion abnormalities can now be visualized directly in the subject's anatomical space, rather than interpolating results from the brain atlas space, and can thereby enhance correlation with other components of an imaging protocol.

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Dataset Information

Longitudinal changes in diffusion tensor-based quantitative MRI in multiple sclerosis.

Objective

Methods

Results

Conclusions

Publications

Longitudinal changes in diffusion tensor-based quantitative MRI in multiple sclerosis.

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